Drug Interactions

The effect a drug has on a person may be different than expected because that drug interacts with

Another drug the person is taking (drug-drug interaction)

Food, beverages, or supplements the person is consuming (drug-nutrient interaction)

Another disease the person has (drug-disease interaction)

The effects of drug interactions are usually unwanted and sometimes harmful. Interactions may increase or decrease the actions of one or more drugs, resulting in side effects or failed treatment.

Drug-Drug Interactions

Drug-drug interactions can involve prescription or nonprescription (over-the-counter) drugs. Types of drug-drug interactions include duplication, opposition (antagonism), and alteration of what the body does to one or both drugs.

Duplication:

When two drugs with the same effect are taken, their side effects may be intensified. Duplication may occur when people inadvertently take two drugs (often at least one is an over-the-counter drug) that have the same active ingredient. For example, people may take a cold remedy and a sleep aid, both of which contain diphenhydramineSome Brand NamesNo US brand name, or a cold remedy and a pain reliever, both of which contain acetaminophenSome Brand NamesTYLENOL. This type of duplication is particularly likely with the use of drugs that contain multiple ingredients or that are sold under brand names (thus appearing to be different but actually containing the same ingredients). Awareness of drug ingredients is important, as is checking each new drug to avoid duplication. For example, many prescription-strength pain relievers contain an opioid plus acetaminophenSome Brand NamesTYLENOL. People taking such a product who do not know its ingredients might take over-the-counter acetaminophenSome Brand NamesTYLENOL for extra relief, risking toxicity.

Similar problems with duplication can arise when two different drugs with the same effect are taken. This is most likely to occur when people see several doctors, obtain prescriptions at more than one pharmacy, or both. Doctors who are not aware of what others have prescribed may inadvertently prescribe similar drugs. For example, excessive sedation and dizziness can occur when two doctors both prescribe a sleep aid or when one prescribes a sleep aid and the other prescribes another drug (such as an antianxiety drug) that has similar sedative effects. People can reduce this risk by keeping each doctor informed about all drugs being taken and by using one pharmacy to obtain all prescriptions. It is helpful to keep an up-to-date written list of all drugs being taken and to bring the list along on each doctor visit. Also, people should not take previously prescribed drugs (such as a sleeping pill or pain reliever) without checking with the doctor or pharmacist because that drug may duplicate or otherwise interact with one of their current drugs.

Opposition (antagonism):

Two drugs with opposing actions can interact, thereby reducing the effectiveness of one or both. For example, nonsteroidal anti-inflammatory drugs (NSAIDs—see see Nonsteroidal Anti-Inflammatory Drugs), such as ibuprofenSome Brand NamesADVILMOTRIN IB, which are taken to relieve pain, may cause the body to retain salt and fluid. Diuretics, such as hydrochlorothiazideSome Brand NamesMICROZIDE and furosemideSome Brand NamesLASIX, help rid the body of excess salt and fluid. If a person takes both types of drug, the NSAID may reduce the diuretic's effectiveness. Certain beta-blockers (such as propranololSome Brand NamesINDERAL), taken to control high blood pressure and heart disease, counteract beta-adrenergic stimulants, such as albuterolSome Brand NamesPROVENTIL-HFAVENTOLIN-HFA, taken to manage asthma. Both types of drugs target the same cell receptors—beta-2 receptors (see Table 1: Targets in The Body: Cell Receptors)—but one type blocks them, and the other stimulates them.

Alteration:

One drug may alter how the body absorbs, distributes, metabolizes, or excretes another drug.

How to Reduce the Risk of Drug-Drug Interactions

Consult the doctor or pharmacist before taking any new drugs, including over-the-counter drugs and dietary supplements, such as medicinal herbs.

Keep a list of all drugs being taken. Periodically discuss this list with the doctor or pharmacist.

Keep a list of all disorders. Periodically discuss this list with the doctor.

Select a pharmacy that provides comprehensive services (including checking for possible interactions) and that maintains a complete drug profile for each person. Have all prescriptions dispensed in this pharmacy.

Learn about the purpose and actions of all drugs prescribed.

Learn about the possible side effects of the drugs.

Learn how to take the drugs, what time of day they should be taken, and whether they can be taken during the same time period as other drugs.

Review the use of over-the-counter drugs with the pharmacist. Discuss any disorders present and any prescription drugs being taken.

Take drugs as instructed.

Report to the doctor or pharmacist any symptoms that might be related to the use of a drug.

If seeing more than one doctor, make sure each doctor knows all the drugs being taken.

Acid-blocking drugs, such as histamine-2 (H2) blockers and proton pump inhibitors, raise the pH of the stomach and decrease absorption of some drugs, such as ketoconazoleSome Brand NamesNIZORAL, a drug for fungal infections.

Many drugs are broken down and inactivated (metabolized) by certain enzymes in the liver. Some drugs affect these liver enzymes, either increasing or decreasing their activity, and may cause another drug to be inactivated more quickly or more slowly than usual. For example, by increasing the activity of liver enzymes, barbiturates such as phenobarbitalSome Brand NamesNo US brand name cause the anticoagulant warfarinSome Brand NamesCOUMADIN to be inactivated more quickly and thus to be less effective when taken during the same time period. Conversely, by decreasing the activity of the enzyme system, drugs such as erythromycinSome Brand NamesERY-TABERYTHROCIN and ciprofloxacinSome Brand NamesCILOXANCIPRO can increase the activity of warfarinSome Brand NamesCOUMADIN, risking bleeding. When drugs that affect liver enzymes are used in people taking warfarinSome Brand NamesCOUMADIN, doctors monitor the people more closely and adjust the dose of warfarinSome Brand NamesCOUMADIN to compensate for this effect. The warfarinSome Brand NamesCOUMADIN dose is adjusted again when other drugs are stopped. Many other drugs affect liver enzymes.

Chemicals in cigarette smoke can increase the activity of some liver enzymes. As a result, smoking decreases the effectiveness of some drugs, including theophyllineSome Brand NamesELIXOPHYLLIN (a drug that widens the airways called a bronchodilator).

Some drugs affect the rate at which the kidneys excrete another drug. For example, large doses of vitamin C increase the urine's acidity and thus may change the rate of excretion and activity of certain drugs. For example, the rate of excretion may be decreased for acidic drugs such as aspirinSome Brand NamesNo US brand name but may be increased for basic drugs such as pseudoephedrineSome Brand NamesAFRINOLSUDAFED.

Because there are so many drug interactions, many doctors and pharmacists reduce the risk of problems by checking reference books and computer software programs when prescribing or dispensing prescriptions for additional drugs. In most pharmacies, drug orders and prescriptions are reviewed using a computer system that automatically checks for drug interactions.

Drug-Nutrient Interactions

Nutrients include food, beverages (including alcohol), and dietary supplements. Consumption of these substances may alter the effects of drugs the person takes.

Food:

Like food, drugs taken by mouth must be absorbed through the lining of the stomach or the small intestine. Consequently, the presence of food in the digestive tract may reduce absorption of a drug. Often, such interactions can be avoided by taking the drug 1 hour before or 2 hours after eating.

Dietary supplements:

Dietary supplements, including medicinal herbs, are products (besides tobacco) that contain a vitamin, mineral, herb, or amino acid and that are intended as a supplement to the normal diet (see see Overview of Medicinal Herbs and Nutraceuticals). Supplements are regulated as foods, not as drugs, so they are not tested as comprehensively. However, they may interact with prescription or over-the-counter drugs. People who take dietary supplements should tell their doctors and pharmacists, so that interactions can be avoided.

Alcohol:

Although many people do not consider alcohol a nutrient, it affects body processes and interacts with many drugs. For example, taking alcohol with the antibiotic metronidazoleSome Brand NamesFLAGYL can cause flushing, headache, palpitations, and nausea and vomiting. Doctors or pharmacists can answer questions about possible alcohol and drug interactions.

Food, even orange juice, coffee, or mineral water, may markedly reduce the absorption and effectiveness of these drugs. AlendronateSome Brand NamesFOSAMAX and risedronateSome Brand NamesACTONEL must be taken with plain water at least 30 minutes before the first food, beverage, or drug of the day is taken, and ibandronateSome Brand NamesBONIVA must be taken at least 1 hour before.

Severe headache and a potentially fatal increase in blood pressure (hypertensive crisis) can occur if people taking an MAO inhibitor (used most often to treat depression) consume these foods. These foods must be avoided.

Foods high in vitamin K (such as broccoli, Brussels sprouts, spinach, and kale)

Such foods may reduce the effectiveness of warfarinSome Brand NamesCOUMADIN, increasing the risk of clotting. Intake of such foods should be limited, and the amount consumed daily should remain constant.

MAO = monoamine oxidase.

Drug-Disease Interactions

Sometimes, drugs that are helpful in one disease are harmful in another disorder. For example, some beta-blockers taken for heart disease or high blood pressure can worsen asthma and make it hard for people with diabetes to tell when their blood sugar is too low. Some drugs taken to treat a cold may worsen glaucoma. People should tell their doctor all of the diseases they have before the doctor prescribes a new drug. Diabetes, high or low blood pressure, an ulcer, glaucoma, an enlarged prostate, poor bladder control, and insomnia are particularly important, because people with such diseases are more likely to have a drug-disease interaction.

Drug-disease interactions can occur in any age group but are common among older people, who tend to have more diseases (see see Aging and Drugs).